1. The Anti-Fibrotic Effects of CG-745, an HDAC Inhibitor, in Bleomycin and PHMG-Induced Mouse Models.
- Author
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Kim YS, Cha H, Kim HJ, Cho JM, and Kim HR
- Subjects
- Animals, Biguanides toxicity, Bleomycin toxicity, Disease Models, Animal, Epithelial-Mesenchymal Transition drug effects, Histone Deacetylase Inhibitors chemistry, Histone Deacetylases chemistry, Humans, Idiopathic Pulmonary Fibrosis chemically induced, Idiopathic Pulmonary Fibrosis pathology, Indoles chemistry, Indoles therapeutic use, Lung pathology, Mice, Pyridones chemistry, Pyridones therapeutic use, Republic of Korea epidemiology, Histone Deacetylase Inhibitors pharmacology, Histone Deacetylases drug effects, Idiopathic Pulmonary Fibrosis drug therapy, Lung drug effects
- Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with poor prognosis and progression to lung fibrosis related to genetic factors as well as environmental factors. In fact, it was discovered that in South Korea many people who used humidifier disinfectants containing polyhexamethylene guanidine (PHMG), died of lung fibrosis. Currently two anti-fibrotic drugs, pirfenidone and nintedanib, have been approved by the FDA, but unfortunately, do not cure the disease. Since the histone deacetylase (HDAC) activity is associated with progression to chronic diseases and with fibrotic phenomena in the kidney, heart and lung tissues, we investigated the anti-fibrotic effects of CG-745, an HDAC inhibitor. After lung fibrosis was induced in two animal models by bleomycin and PHMG instillation, the regulation of fibrosis and epithelial mesenchymal transition (EMT)-related markers was assessed. CG-745 exhibited potent prevention of collagen production, inflammatory cell accumulation, and cytokines release in both models. Additionally, N-cadherin and vimentin expression were lowered significantly by the treatment of CG-745. The anti-fibrotic effects of CG-745 proven by the EMT regulation may suggest a potential therapeutic effect of CG-745 on lung fibrosis.
- Published
- 2019
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